P2‐162: EXERCISE‐LINKED FNDC5/IRISIN CORRECTS SYNAPTIC PLASTICITY AND MEMORY DEFECTS IN MOUSE MODELS OF ALZHEIMER'S DISEASE
Bibliographic record
Abstract
Defects in brain hormonal signaling have been associated with synapse and memory failure in Alzheimer's disease (AD). Irisin is an exercise-induced myokine released on cleavage of the precursor protein fibronectin type III domain-containing protein 5 (FNDC5), also present in the hippocampus. Given that exercise has been associated with neuroprotection in AD, we tested whether FNDC5/irisin would be neuroprotective in AD models and further mediate the beneficial effects of exercise in AD mice. We used ELISA and Western blotting to determine brain levels of FNDC5/irisin in the postmortem AD brains and in experimental models of AD. We further employed pharmacological, molecular and behavioural approaches to investigate the potential neuroprotective actions of FNDC5/irisin in AD mice. We show that FNDC5/irisin levels are reduced in the hippocampi of AD patients and experimental models. Downregulation of brain FNDC5/irisin levels impairs long-term potentiation and novel object recognition memory in mice. Conversely, overexpression of FNDC5/irisin in the brain rescues synaptic plasticity and memory in mouse models of AD. Peripheral overexpression of FNDC5/irisin also rescues memory impairment, whereas blockade of peripheral or brain FNDC5/irisin attenuates the neuroprotective actions of physical exercise on synaptic plasticity and memory in AD mice. Our results indicate that FNDC5/irisin has neuroprotective properties in AD mice and supports the notion that this hormone mediates at least some of the beneficial actions of physical exercise in the brain.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".